Project Summary/Abstract. Catalytic Asymmetric Hydroboration: Uncapping the Potential with Two- Point Binding Substrates Developing efficient methods for the reliable, stereocontrolled synthesis of small molecules via asymmetric catalysis is central to providing the means to prepare potential mechanistic probes and pharmaceuticals. These are essential tools that enable the better understanding and control of biological processes relevant to human health. The development of new catalytic asymmetric reactions is therefore of both practical and fundamental importance to the NIH mission. Chiral organoboranes are finding increasing use as synthetic intermediates en route to other useful functionality via stereospecific functional group interconversion, as reagents for asymmetric synthesis, and synthetic targets for pharmaceutical applications. The stereochemistry of the carbon-boron bond is exploited via stereospecific transmetallation or conversion to other useful functional groups. Organoboranes are therefore seen as important intermediates for incorporating a variety of functional groups with defined stereochemistry in natural product, pharmaceutical intermediate, and materials synthesis. Recent breakthroughs in the development of methods for the stereospecific conversion of carbon-boron to carbon- carbon bonds increase the demand for efficient methods to synthesize chiral organoboronates. The proposed studies build on recent breakthroughs in the CAHB of two-point binding substrates. The key innovation is in focusing on the directed CAHB of two-point binding substrates leading to successful catalysts derived from simple, readily accessible monodentate phosphite and phosphoramidite ligands. This is in contrast to prior approaches that focused on a more limited range of substrates, i.e., vinylarenes or strained alkenes, using catalysts employing more complex, chelating ligands. The specific aims of the proposal are to (i) expand the scope of directed-CAHB by: building on the results obtained for regio- and enantioselective borylation of ?,?-unsaturated substrates; building on promising preliminary results for substrates in which the directing group is further removed from the alkene; and further developing an understanding of the mechanism and the potential for enhanced regiocontrol and (ii) expand the scope of transformations stemming from interrupted-CAHB catalysis by: expanding the substrate scope for borane-promoted, rhodium-catalyzed catalytic asymmetric hydrogenation (CAH); further delineating the mechanism of a borane-promoted CAH via interrupted CAHB; and expanding to other metal catalyst systems and exploring other ways to exploit the reactivity of the presumed metal-boryl intermediates generated by CAHB. A greater variety of chiral organoboronates will be made readily available as a result of this project.